chr19-18579020-T-C

Variant names:

• chr19-18579020-T-C
• rs2057649
• ENST00000594325.1:n.232+4550A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000594325.1(CRLF1):​n.232+4550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,976 control chromosomes in the GnomAD database, including 19,029 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19029 hom., cov: 31)
• Consequence: CRLF1 ENST00000594325.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 13 publications found

Genes affected

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

CRLF1 Gene-Disease associations (from GenCC):

• Cold-induced sweating syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cold-induced sweating syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• idiopathic achalasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000594325.1	n.232+4550A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72182 AN: 151860 Hom.: 19014 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72220 AN: 151976 Hom.: 19029 Cov.: 31 AF XY: 0.480 AC XY: 35618 AN XY: 74272

African (AFR) AF: 0.233 AC: 9672 AN: 41448

American (AMR) AF: 0.540 AC: 8238 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3354 AN: 5166

South Asian (SAS) AF: 0.473 AC: 2281 AN: 4822

European-Finnish (FIN) AF: 0.616 AC: 6495 AN: 10538

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38844 AN: 67978

Other (OTH) AF: 0.502 AC: 1058 AN: 2106

Alfa AF: 0.533 Hom.: 33908

Bravo AF: 0.462

Asia WGS AF: 0.569 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.52
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2057649; hg19: chr19-18689830;